The presently disclosed subject matter relates to an apparatus for evaluating a vascular endothelial function in which the evaluation similar to that obtained in a measurement using an ultrasonic echo system is enabled without using an ultrasonic echo system or the like.
Recently, researches that arteriosclerosis develops while showing deterioration of the vascular endothelial function as the initial phase have been conducted. In order to prevent arteriosclerosis, techniques and apparatuses for evaluating the vascular endothelial function have been developed.
As a reliable technique for evaluating the vascular endothelial function, there is an apparatus called an FMD (Flow-Mediated Dilation) measurement system. In the apparatus, measurement is performed in the following manner. A cuff which is similar to that for measuring the blood pressure is attached to the arm of the subject. After occlusion of the artery is performed for a constant time of about five minutes at a pressure which is higher than the maximal blood pressure of the subject, the occlusion of the artery is released. At about three minutes after the release of the occlusion of the artery, the vessel diameter at the upstream or downstream of the cuff is measured by an ultrasonic echo system. Based on the time-dependent change rate of the vessel diameter, the vascular endothelial function is evaluated.
In the case of a normal vessel, the production of NO which is a vasodepressor material from vascular endothelial cells is promoted by shear stress of the inner wall of the vessel due to a blood flow immediately after the occlusion of the artery. As a result, the vessel diameter is expanded. By contrast, in the case where a disorder exists in the vascular endothelial function, the degree of the expansion of the vessel diameter is decreased. When the change in vessel diameter before and after the occlusion of the artery is measured, therefore, it is possible to evaluate the vascular endothelial function.
The evaluation technique by the FMD measurement system requires skills in measurement of the vessel diameter by an ultrasonic echo system, and is difficult to handle. Furthermore, there is a problem in that the technique requires a large-scale apparatus and lacks in simplicity.
By contrast, as a technique using a simple configuration, there is a technique using a cuff pressure. In the technique, the cuff pressure is maintained at a predetermined pressure which is higher than the maximal blood pressure, thereafter rapidly lowered, maintained at another predetermined pressure which is higher than the minimal blood pressure and lower than the mean blood pressure, and, during when the cuff pressure is maintained at the other predetermined pressure, a ratio of a cuff pressure peak value of a first pulse wave which initially appears to the maximal cuff pressure peak value which thereafter appears is calculated, thereby enabling the vascular endothelial function to be evaluated (see JP-A-2007-209492).
As a technique in which an index of the vascular endothelial function can be accurately measured by a simple method, there is a technique in which pressure and volume pulse waves of a vessel to be measured are measured, a ratio of variations of the pulse waves per unit time is obtained, and, with respect to the third root of the maximum value of the ratio of variations of one heartbeat cycle at rest, a ratio to a value after release of occlusion of the artery is calculated as the degree of vasodilation (see JP-A-2006-181261).
There is another technique in which, based on the time-dependent change of posterior pulse wave information indicating a feature of the posterior half portion which is after the peak of a pulse wave reflecting variations of the vessel diameter, it is determined whether the function of vascular endothelial cells is normal or not (see Japanese Patent No. 3,632,014).
There is a further technique in which a digit probe for measuring a change of the peripheral arterial pulsatile flow is attached to a finger tip, occlusion of the artery is performed for a constant time period while attaching a cuff to the same finger tip, and a change of the peripheral arterial tone before and after the occlusion of the artery is monitored by the digit probe (see Japanese Patent No. 4,049,671).
In the FMD method, the measurement is performed by using the ultrasonic echo system, and skills are required to measure the vessel diameter. In the presently disclosed subject matter, by contrast, a change in vascular volume before and after the pressure stimulation is measured, so that information which is equivalent to that obtained in the FMD method that is a reliable related art technique can be easily obtained, and the measurement can be performed by a technique and configuration which are similar to those of the blood pressure measurement that is currently widely performed, so that skills are not required.
In the technique disclosed in JP-A-2007-209492, the pressurization periods for the pressure stimulation and the pulse wave measurement are continuous to each other. Although the pressurization for the pulse wave measurement is lower than the artery mean blood pressure, the vein blood flow is blocked, and hence the burden on the subject is large. In the presently disclosed subject matter, by contrast, an idle period when the cuff pressurization is stopped exists between the pressure stimulation and the pulse wave measurement. Therefore, a continuous vessel blocking period is kept to the minimum, so that the burden on the subject can be reduced.
In the technique disclosed in JP-A-2006-181261, in addition to the cuff for the pressure stimulation, a sensor for measuring the volume and pressure pulse waves must be disposed. Therefore, the operation is complicated. In the presently disclosed subject matter, by contrast, a sensor other than the attachment of the cuff is not necessary. Consequently, the presently disclosed subject matter is advantageous in operation.
In the technique disclosed in Japanese Patent No. 3,632,014, a reflected wave component which is contained in the pressure pulse wave, and which is originated from peripheral vessels is measured. Measurement of the reflected wave component and calculation of an amplitude augmentation factor AI necessitate complicated waveform recognizing and calculating processes, and an analyzing unit must have a high processing capacity. In the presently disclosed subject matter, by contrast, it is requested only to measure the waveform of a pulse wave, and hence an analyzing unit is not required to have a high processing capacity.
The vascular compliance is changed by the blood pressure. When the blood pressure is high, the vessel wall is in a state where the wall is extended in the circumferential direction and hardened, and the compliance is low. Conversely, when the blood pressure is low, a force acting on the vessel wall is small. Therefore, the vessel wall is extended in a smaller degree in the circumferential direction, and the compliance is high. All of the techniques disclosed in JP-A-2007-209492, JP-A-2006-181261 and Japanese Patent No. 3,632,014 have a problem in that the measured vessel information is inevitably affected by the intravascular pressure, i.e., the blood pressure.
In the technique disclosed in Japanese Patent No. 4,049,671, a change of the peripheral arterial tone is monitored by the digit probe. In the case where amplitudes of pulse waves are compared to each other, however, the possibility that unwanted influences are included is high. Particularly, the peripheral arterial tone is caused also by the sympathetic control. Consequently, there is a problem in that the technique cannot always correctly detect the vascular endothelial function.
In the related art, the cuff pressure indicating the maximum pulse wave amplitude corresponds to the mean blood pressure. Irrespective of the level of the blood pressure, when a vessel is compressed by a cuff at a pressure which is equal to the mean blood pressure, the pressures internal and external of the vessel counteract each other, and the force acting in the circumferential direction of the vessel wall is minimized. The maximum pulse wave amplitude which is measured in the presently disclosed subject matter is always measured in a state where the force acting in the circumferential direction of the vessel wall is minimum, and therefore the influence of the level of the blood pressure on the measurement result is reduced. It can be said that a change in vessel diameter in this state indicates the characteristics of the vessel wall itself.
In view of the above-discussed circumstances, the inventors have proposed an apparatus and the like in which a cuff is wrapped around a part of the body such as an arm, occlusion of the artery is performed for a predetermined time period by using the cuff, the pulse wave is detected by using the cuff at the same position before and after the occlusion of the artery or the like, and the detected pulse wave is analyzed to evaluate the vascular endothelial function (see JP-A-2009-273870 and JP-A-2011-56200).
It has been proved that, according to the apparatus, the vascular endothelial function can be adequately evaluated by using a cuff. Thereafter, the inventors have intensively studied, and obtained the conclusion that, in the techniques disclosed in JP-A-2009-273870 and JP-A-2011-56200, the influence due to the blood pressure can be reduced by measuring the maximum pulse wave amplitude in the case where the cuff pressure is changed, but this measurement is probably performed merely on one of the viscoelastic characteristics of the vessel. When a change occurs in the vessel wall viscosity, therefore, a change appears in the response characteristics of the vessel wall, in addition to a change in the pulse wave amplitude. In the techniques disclosed in JP-A-2009-273870 and JP-A-2011-56200, however, there is a possibility that such a change cannot be sufficiently captured. It has been considered that a comparison of viscoelastic indexes of the vessel (hereinafter, such an index is referred to as “vessel viscoelastic index”) other than the maximum pulse wave amplitude is effective in solving the problem.
In a case where the structure of the artery wall is expressed by the Voigt model, the following expression holds for the stress f and the distortion x:f=ex+r(dx/dt)  (1)where e is the elastic constant and r is the viscosity constant.
It is considered that the distortion x in Expression (1) corresponds to the change in the vessel diameter in the techniques disclosed in JP-A-2009-273870 and JP-A-2011-56200, and the techniques disclosed in JP-A-2009-273870 and JP-A-2011-56200 in which the ratio of maximum pulse wave amplitudes are obtained are those mainly related to indexes of the portion of Expression (1) indicating all of the vessel viscoelastic indexes, excluding the derivative term of the right side. Therefore, it is requested to develop an apparatus for evaluating a vascular endothelial function which uses the indexes related to Expression (1) indicating all of the vessel viscoelastic indexes, excluding the maximum pulse wave amplitude.
The related-art FMD measures the DC component (the distortion x in Expression (1)) of the vessel diameter in synchronization with the QRS of an electrocardiogram, in principle does not measure the pulsation component, and therefore is not affected by the viscosity of the vessel wall. As apparent from Expression (1), however, the evaluation technique in the presently disclosed subject matter which uses the vessel viscoelastic indexes, and which is related to the vascular endothelial function is affected by the viscosity (r(dx/dt) in Expression (1)) of the vessel wall. When an apparatus for evaluating a vascular endothelial function in which an evaluation similar to that obtained in a measurement using an ultrasonic echo system is enabled is to be developed, therefore, the influence of the viscosity must be reduced as far as possible.
FIG. 9 shows results of measurements of changes of the elasticity and the viscosity in the vasolidation before and after the pressure stimulation, by the related-art FMD. According to FIG. 9, it is seen that the elasticity after the pressure stimulation is decreased as compared to that before the pressure stimulation, and the viscosity after the pressure stimulation is increased as compared to that before the pressure stimulation.
FIG. 10 shows examples of the amplitude waveform of the pulse wave in measurements in cases where only the elasticity was decreased, and where the elasticity was decreased and at the same time the viscosity was increased. According to FIG. 10, when only the elasticity is decreased, only the amplitude of the pulse wave is increased, and it is estimated that, when the amplitude of the pulse wave is measured, the vascular endothelial function can be captured. As shown in the lower portion of FIG. 10, it is seen that, when the elasticity is decreased and the viscosity is simultaneously increased, a time lag occurs in the amplitude change. As a result, it is suggested that, when the elasticity is decreased and the viscosity is simultaneously increased, sufficient determination cannot be performed by means of a measurement of the amplitude change.